Synthesis, Nicotinic Acetylcholine Receptor Binding, and Pharmacological Properties of 3'-(substituted Phenyl)deschloroepibatidine Analogs

Overview

Journal Bioorg Med Chem

Specialties Biochemistry
Chemistry

Date 2007 Oct 30

PMID 17964169

Citations 10

Authors

F Ivy Carroll

Yasuno Yokota

Wei Ma

Jeffrey R Lee

Lawrence E Brieaddy

Jason P Burgess

Hernan A Navarro

M I Damaj

Billy R Martin

Affiliations

Soon will be listed here.

Abstract

A series of 3'-(substituted phenyl)deschloroepibatidine analogs (5a-j) were synthesized. The alpha4beta2( *) and alpha7 nicotinic acetylcholine receptor (nAChR) binding properties and functional activity in the tail-flick, hot-plate, locomotor, and body temperature tests in mice of 5a-j were compared to those of the nAChR agonist, nicotine (1), epibatidine (4), and deschloroepibatidine (13), the partial agonist, varenicline (3), and the antagonist 2'-fluoro-3'-(substituted phenyl)deschloroepibatidine analogs (7a-j). Unlike epibatidine and deschloroepibatidine, which are potent agonists in the tail-flick test, 5a-k show no or very low antinociceptive activity in the tail-flick or hot-plate test. However, they are potent antagonists in nicotine-induced antinociception in the tail-flick test, but weaker than the corresponding 2'-fluoro-3'-(substituted phenyl)deschloroepibatidines.

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